Faculty Opinions recommendation of Genetic Variability of Hepatitis C Virus (HCV) 5' Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin.

ABSTRACT Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2α phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of >4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of >4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of ≤40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (>4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.

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Hepatitis C virus genotype 1: How genetic variability of the core protein affects the response to pegylated-interferon and ribavirin therapy

Journal of Medical Virology ◽

10.1002/jmv.23823 ◽

2013 ◽

Vol 86 (2) ◽

pp. 224-234 ◽

Cited By ~ 3

Author(s):

F.S. Alhamlan ◽

M.N. Al-Ahdal ◽

N.Z. Khalaf ◽

A.A. Abdo ◽

F.M. Sanai ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Genetic Variability ◽

Core Protein ◽

Pegylated Interferon ◽

Genotype 1 ◽

Virus Genotype ◽

The Core

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Genetic variability of the core protein in hepatitis C virus genotype 4 in Saudi Arabian patients and its implication on pegylated interferon and ribavirin therapy

Journal of Translational Medicine ◽

10.1186/1479-5876-12-91 ◽

2014 ◽

Vol 12 (1) ◽

pp. 91 ◽

Cited By ~ 7

Author(s):

Fatimah S Alhamlan ◽

Mohammed N Al-Ahdal ◽

Nisreen Z Khalaf ◽

Ayman A Abdo ◽

Faisal M Sanai ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Genetic Variability ◽

Core Protein ◽

Saudi Arabian ◽

Pegylated Interferon ◽

Virus Genotype ◽

Genotype 4 ◽

The Core

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Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.251.a2a ◽

2016 ◽

Vol 25 (1) ◽

pp. 15-24 ◽

Cited By ~ 2

Author(s):

Tim Zimmermann ◽

Dietrich Hueppe ◽

Stefan Mauss ◽

Peter Buggisch ◽

Heike Pfeiffer-Vornkahl ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Therapy ◽

Interferon Alpha ◽

Virological Response ◽

Sustained Viral Response ◽

Pegylated Interferon ◽

Genotype 1 ◽

Pegylated Interferon Alpha ◽

Viral Response

Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.

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